Basic research on neonatal Fc receptor (FcRn) affinity to establish half-life extension technology of therapeutic antibodies

Research Project

Project/Area Number	15K08087
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Medical pharmacy
Research Institution	National Institute of Health Sciences
Principal Investigator	Suzuki Takuo 国立医薬品食品衛生研究所, 生物薬品部, 主任研究官 (10415466)
Co-Investigator(Kenkyū-buntansha)	橋井則貴国立医薬品食品衛生研究所, 生物薬品部, 室長 (20425672)
Project Period (FY)	2015-04-01 – 2018-03-31
Project Status	Completed (Fiscal Year 2017)
Budget Amount *help	¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000) Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	FcRn / 抗体医薬品 / 表面プラズモン共鳴 / Fcγ受容体 / 半減期延長 / アミノ酸改変 / HDX/MS / 水素重水素交換／質量分析
Outline of Final Research Achievements	Therepeutic antibodies are protected from degradation by binding to neonatal Fc receptor (FcRn) in endosome and are recycled into plasma, thereby having long half-lives. To prolong the half-lives additionally with the aim of reducing dose and frequency, amino acids-substituted antibodies having high affinity to FcRn are being developed. However, there are cases that the half-lives of the antibodies are not prolonged. As basic researches on neonatal Fc receptor (FcRn) affinity to establish half-life extension technology of therapeutic antibodies, we performed the studies on the binding between FcRn and amino acids-substituted antibodies, and investigated the changes of the conformation and function of IgG (i.e. binding to Fc gamma receptors) by amino acids substitution for raising the affinity to FcRn.